M. Kara Bucci

Advances in radiation therapy: conventional to 3D, to IMRT, to 4D, and beyond.

Modern advances in computers have fueled parallel advances in imaging technologies. The improvements in imaging have in turn allowed a higher level of complexity to be incorporated into radiotherapy treatment planning systems. As a result of these changes, the delivery of radiotherapy evolved from therapy designed based primarily on plain (two dimensional) x‐ray images and hand calculations to three‐dimensional x‐ray based images incorporating increasingly complex computer algorithms. More recently, biologic variables based on differences between tumor metabolism, tumor antigens, and normal tissues have been incorporated into the treatment process. In addition, greater awareness of the challenges to the accuracy of the treatment planning process, such as problems with set‐error and organ movement, have begun to be systematically addressed, ushering in an era of so‐called Four‐Dimensional Radiotherapy. This review article discusses how these advances have changed the way the most common neoplasms are treated now and will be treated in the near future.

Stereotactic Body Radiation Therapy in Centrally and Superiorly Located Stage I or Isolated Recurrent Non–Small-Cell Lung Cancer

PURPOSE To evaluate the efficacy and adverse effects of image-guided stereotactic body radiation therapy (SBRT) in centrally/superiorly located non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS We delivered SBRT to 27 patients, 13 with Stage I and 14 with isolated recurrent NSCLC. A central/superior location was defined as being within 2 cm of the bronchial tree, major vessels, esophagus, heart, trachea, pericardium, brachial plexus, or vertebral body, but 1 cm away from the spinal canal. All patients underwent four-dimensional computed tomography-based planning, and daily computed tomography-on-rail guided SBRT. The prescribed dose of 40 Gy (n = 7) to the planning target volume was escalated to 50 Gy (n = 20) in 4 consecutive days. RESULTS With a median follow-up of 17 months (range, 6-40 months), the crude local control at the treated site was 100% using 50 Gy. However, 3 of 7 patients had local recurrences when treated using 40 Gy. Of the patients with Stage I disease, 1 (7.7%) and 2 (15.4%) developed mediastinal lymph node metastasis and distant metastases, respectively. Of the patients with recurrent disease, 3 (21.4%) and 5 (35.7%) developed mediastinal lymph node metastasis and distant metastasis, respectively. Four patients (28.6%) with recurrent disease but none with Stage I disease developed Grade 2 pneumonitis. Three patients (11.1%) developed Grade 2-3 dermatitis and chest wall pain. One patient developed brachial plexus neuropathy. No esophagitis was noted in any patient. CONCLUSIONS Image-guided SBRT using 50 Gy delivered in four fractions is feasible and resulted in excellent local control.

PATTERNS OF FAILURE AFTER COMBINED-MODALITY APPROACHES INCORPORATING RADIOTHERAPY FOR SINONASAL UNDIFFERENTIATED CARCINOMA OF THE HEAD AND NECK

PURPOSE To report the clinical outcome of patients treated with combined-modality approaches for sinonasal undifferentiated carcinoma (SNUC) of the head and neck. METHODS AND MATERIALS The records of 21 patients with SNUC treated with curative intent at the University of California, San Francisco between 1990 and 2004 were analyzed. Patient age ranged from 33 to 71 years (median, 47 years). Primary tumor sites included the nasal cavity (11 patients), maxillary sinus (5 patients), and ethmoid sinus (5 patients). All patients had T3 (4 patients) or T4 (17 patients) tumors. Local-regional treatment included surgery followed by postoperative radiotherapy (PORT) with or without adjuvant chemotherapy for 17 patients; neoadjuvant chemoradiotherapy followed by surgery for 2 patients; and definitive chemoradiotherapy for 2 patients. Median follow-up among surviving patients was 58 months (range, 12-70 months). RESULTS The 2- and 5-year estimates of local control were 60% and 56%, respectively. There was no difference in local control according to initial treatment approach, but among the 19 patients who underwent surgery the 5-year local control rate was 74% for those with gross tumor resection, compared with 24% for those with subtotal tumor resection (p = 0.001). The 5-year rates of overall and distant metastasis-free survival were 43% and 64%, respectively. Late complications included cataracts (2 patients), lacrimal stenosis (1 patient), and sino-cutaneous fistula (1 patient). CONCLUSION The suboptimal outcomes suggest a need for more effective therapies. Gross total resection should be the goal of all treatments whenever possible.

Daily alignment results of in-room computed tomography-guided stereotactic body radiation therapy for lung cancer

PURPOSE To determine the extent of interfractional setup errors and day-to-day organ motion errors by assessing daily bone alignment results and changes in soft tissue tumor position during hypofractionated, in-room computed tomography (CT)-guided stereotactic body radiation therapy (SBRT) of lung cancer. METHODS AND MATERIALS Daily alignment results during SBRT were analyzed for 117 tumors in 112 patients. Patients received 40-50 Gy of SBRT in four to five fractions using an integrated CT-LINAC system. The free-breathing CT scans acquired during treatment setup were retrospectively realigned to match with each of the bony references and the gross tumor volume (GTV) defined on the reference CT by rigid-body registration, and the daily deviations were calculated. RESULTS The mean magnitude (± SD) three-dimensional shift from the initial skin marks to the final bone-aligned positions was 9.4 ± 5.7 mm. The mean daily GTV deviation from the bone position was 0.1 ± 3.8 mm in the anterior-posterior direction, -0.01 ± 4.2 mm in the superior-inferior direction, and 0.2 ± 2.5 mm in the lateral direction. A clinically noteworthy trend (net change >5 mm in any direction) in GTV position relative to the bone was observed in 23 cases (20%). CONCLUSIONS Soft tissue target position can change significantly beyond the motion envelope defined in the original internal target volume in four-dimensional CT-based treatment planning for SBRT of lung cancer. Additional margin should be considered for adequate coverage of interfractional changes.

Comparison of Rigid and Adaptive Methods of Propagating Gross Tumor Volume Through Respiratory Phases of Four-Dimensional Computed Tomography Image Data Set

PURPOSE To compare three different methods of propagating the gross tumor volume (GTV) through the respiratory phases that constitute a four-dimensional computed tomography image data set. METHODS AND MATERIALS Four-dimensional computed tomography data sets of 20 patients who had undergone definitive hypofractionated radiotherapy to the lung were acquired. The GTV regions of interest (ROIs) were manually delineated on each phase of the four-dimensional computed tomography data set. The ROI from the end-expiration phase was propagated to the remaining nine phases of respiration using the following three techniques: (1) rigid-image registration using in-house software, (2) rigid image registration using research software from a commercial radiotherapy planning system vendor, and (3) rigid-image registration followed by deformable adaptation originally intended for organ-at-risk delineation using the same software. The internal GTVs generated from the various propagation methods were compared with the manual internal GTV using the normalized Dice similarity coefficient (DSC) index. RESULTS The normalized DSC index of 1.01 +/- 0.06 (SD) for rigid propagation using the in-house software program was identical to the normalized DSC index of 1.01 +/- 0.06 for rigid propagation achieved with the vendors research software. Adaptive propagation yielded poorer results, with a normalized DSC index of 0.89 +/- 0.10 (paired t test, p <0.001). CONCLUSION Propagation of the GTV ROIs through the respiratory phases using rigid- body registration is an acceptable method within a 1-mm margin of uncertainty. The adaptive organ-at-risk propagation method was not applicable to propagating GTV ROIs, resulting in an unacceptable reduction of the volume and distortion of the ROIs.

Recurrent salivary gland carcinomas treated by surgery with or without intraoperative radiation therapy

The optimal treatment for patients with locally recurrent carcinomas of the salivary glands is unclear.

Defining internal target volume using positron emission tomography for radiation therapy planning of moving lung tumors

Substantial disagreement exists over appropriate PET segmentation techniques for non‐small cell lung cancer. Currently, no segmentation algorithm explicitly considers tumor motion in determining tumor borders. We developed an automatic PET segmentation model as a function of target volume, motion extent, and source‐to‐background ratio (the VMSBR model). The purpose of this work was to apply the VMSBR model and six other segmentation algorithms to a sample of lung tumors. PET and 4D CT were performed in the same imaging session for 23 patients (24 tumors) for radiation therapy planning. Internal target volumes (ITVs) were autosegmented on maximum intensity projection (MIP) of cine CT. ITVs were delineated on PET using the following methods: 15%, 35%, and 42% of maximum activity concentration, standardized uptake value (SUV) of 2.5 g/mL, 15% of mean activity concentration plus background, a linear function of mean SUV, and the VMSBR model. Predicted threshold values from each method were compared to measured optimal threshold values, and resulting volume magnitudes were compared to cine‐CT‐derived ITV Correlation between predicted and measured threshold values ranged from slopes of 0.29 for the simplest single‐threshold techniques to 0.90 for the VMSBR technique. R2 values ranged from 0.07 for the simplest single‐threshold techniques to 0.86 for the VMSBR technique. The VMSBR segmentation technique that included volume, motion, and source‐to‐background ratio, produced accurate ITVs in patients when compared with cine‐CT‐derived ITV. PACS number: 87.57.nm